Identification and targeting of long-term tumor propagating cells in small cell lung cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Julien Sage
PROVIDER: E-GEOD-72406 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:FACS sorted TPCs (CD24HighCD44LowEpCAMHigh) and non-TPCs (CD24Low, CD24HighCD44High, and CD24HighCD44LowEpCAMLow) from mouse primary SCLC tumors We used microarrays to identify genes that are differentially expressed in TPCs versus non-TPCs.
2016-06-15 | GSE72406 | GEO
Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) remains among the most aggressive human cancers. Tumor progression and aggressiveness in SCC are largely driven by Tumor Propagating Cells (TPCs). Aerobic glycolysis, also known as the Warburg Effect, represents a characteristic of many cancers, yet whether this adaptation is functionally important in SCC, and at which stage, remains poorly understood. Here, we show that the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) is a robust tumor suppressor in SCC, acting as a modulator of glycolysis in these tumors. Remarkably, rather than a late adaptation, we find enhanced glycolysis specifically in TPCs. More importantly, using single cell RNA sequencing of TPCs, we identify a subset of TPCs with higher glycolysis and enhanced pentose phosphate pathway and glutathione metabolism, characteristics that are strongly associated with a better antioxidant response. Altogether, our studies uncover enhanced glycolysis as a main driver in SCC, and, more importantly, identify a subset of TPCs as the cell-of-origin for the Warburg effect, defining metabolism as a key feature of intra-tumor heterogeneity.
2021-01-14 | GSE147031 | GEO
Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) remains among the most aggressive human cancers. Tumor progression and aggressiveness in SCC are largely driven by Tumor Propagating Cells (TPCs). Aerobic glycolysis, also known as the Warburg Effect, represents a characteristic of many cancers, yet whether this adaptation is functionally important in SCC, and at which stage, remains poorly understood. Here, we show that the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) is a robust tumor suppressor in SCC, acting as a modulator of glycolysis in these tumors. Remarkably, rather than a late adaptation, we find enhanced glycolysis specifically in TPCs. More importantly, using single cell RNA sequencing of TPCs, we identify a subset of TPCs with higher glycolysis and enhanced pentose phosphate pathway and glutathione metabolism, characteristics that are strongly associated with a better antioxidant response. Altogether, our studies uncover enhanced glycolysis as a main driver in SCC, and, more importantly, identify a subset of TPCs as the cell-of-origin for the Warburg effect, defining metabolism as a key feature of intra-tumor heterogeneity.
2021-01-14 | GSE115953 | GEO
Project description:We aimed to analyze the transcriptional profile of full-blown murine lung adenocarcinomas driven by K-RasG12V oncogene. We used a GEM model of lung adenocarcinoma driven by a resident K-RasG12V oncogene. On average, tumors were collected 10 months after Adeno-CRE infection.
2015-12-14 | E-GEOD-65257 | biostudies-arrayexpress
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma. Murine soft tissue sarcomas (n = 17) were compared to normal muscle (n = 4). Tumors were isolated surgically from soft tissue sarcomas generated by conditional Kras and p53 alleles. Tumors were induced using an adenovirus expressing Cre recombinase. Normal muscle samples were isolated from mice of the same genotype without tumor induction.
2010-03-03 | E-GEOD-16779 | biostudies-arrayexpress
Project description:Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies. 3'end RNA sequencing
2014-04-14 | E-GEOD-54791 | biostudies-arrayexpress
Project description:Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies.
2014-04-14 | GSE54791 | GEO
Project description:Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies.
2014-04-10 | GSE54047 | GEO
Project description:Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies. Histone modification profiling for H3K27ac and transcription factors in glioblastoma cell line reprogramming
2014-04-10 | E-GEOD-54047 | biostudies-arrayexpress
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated the histology, gene expression and microenvironment found in human disease. Lkb1/Pten-null (LP) tumors expressed the squamous markers Krt5, p63 and Sox2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. Sca1+/Ngfr+ fractions were enriched for tumor propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and Ngfr+ cells in human SCCs highly expressed Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells. Kras tumor stroma cells and LP tumor stroma cells were sorted by FACS, the cells were gated as EpCAM-/CD45+/CD31+
2014-01-24 | E-GEOD-54352 | biostudies-arrayexpress